Sex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging

• Published in: Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2020-03, Vol.30 (3), p.1345-1356
• Main Authors: Baldinger-Melich, Pia, Urquijo Castro, Maria F, Seiger, René, Ruef, Anne, Dwyer, Dominic B, Kranz, Georg S, Klöbl, Manfred, Kambeitz, Joseph, Kaufmann, Ulrike, Windischberger, Christian, Kasper, Siegfried, Falkai, Peter, Lanzenberger, Rupert, Koutsouleris, Nikolaos
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhz170

Abstract Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR]  0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P